Effects of Prolonged Whey Protein Supplementation and Resistance Training on Biomarkers of Vitamin B12 Status: A 1-Year Randomized Intervention in Healthy Older Adults (the CALM Study)

Nutrients. 2020 Jul 7;12(7):2015. doi: 10.3390/nu12072015.


We investigated the effect of long-term whey supplementation on biomarkers of B12 status in healthy older adults subjected to different schemes of supplements and exercise. The total study population examined at baseline consisted of 167 healthy older adults (age ≥ 65 year) who were randomized to 1-y intervention with two daily supplements of (1) whey protein (3.1 µg B12/day) (WHEY-ALL), (2) collagen (1.3 µg B12/day) (COLL), or (3) maltodextrin (0.3 µg B12/day) (CARB). WHEY-ALL was comprised of three groups, who performed heavy resistance training (HRTW), light resistance training (LITW), or no training (WHEY). Dietary intake was assessed through 3-d dietary records. For the longitudinal part of the study, we included only the participants (n = 110), who met the criteria of ≥ 50% compliance to the nutritional intervention and ≥ 66% and ≥ 75% compliance to the heavy and light training, respectively. Fasting blood samples collected at baseline and 12 months and non-fasting samples collected at 6 and 18 months were examined for methylmalonic acid, B12 and holotranscobalamin. At baseline, the study population (n = 167) had an overall adequate dietary B12 intake of median (range) 5.3 (0.7-65) µg/day and median B12 biomarker values within reference intervals. The whey intervention (WHEY-ALL) caused an increase in B12 (P < 0.0001) and holotranscobalamin (P < 0.0001). In addition, methylmalonic acid decreased in the LITW group (P = 0.04). No change in B12 biomarkers was observed during the intervention with collagen or carbohydrate, and the training schedules induced no changes. In conclusion, longer-term daily whey intake increased plasma B12 and holotranscobalamin in older individuals. No effect of intervention with collagen or carbohydrate or different training regimes was observed. Interestingly, the biomarkers of B12 status appeared to be affected by fasting vs. non-fasting conditions during sample collection.

Keywords: carbohydrate; cobalamin; collagen; collagen protein hydrolysate; exercise; fasting versus non-fasting blood samples; intervention; maltodextrin; vitamin B12; whey; whey protein hydrolysate.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Collagen / administration & dosage
  • Denmark
  • Diet Records
  • Dietary Carbohydrates / administration & dosage
  • Dietary Supplements*
  • Exercise
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Methylmalonic Acid / blood
  • Nutritional Status
  • Polysaccharides / administration & dosage
  • Resistance Training / methods*
  • Transcobalamins / analysis
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / blood*
  • Vitamin B 12 Deficiency / blood
  • Whey Proteins / administration & dosage*


  • Biomarkers
  • Dietary Carbohydrates
  • Polysaccharides
  • Transcobalamins
  • Whey Proteins
  • maltodextrin
  • Methylmalonic Acid
  • Collagen
  • Vitamin B 12